tbuckley/cabot-search huggingface dataset:
QOL-30. Positive Effects of a psychological preparation program for MRI in children with cognitive issues – how to best meet the patients’ needs
Authors: Liesa Josephine Weiler-Wichtl, Jonathan Fries, Verena Fohn-Erhold, Agathe Schwarzinger, Angelika Holzer, Thomas Pletschko, Julia Furtner, Daniela Preyer, Paul Baer, Irene Slavc, Andreas Peyrl, Amedeo Azizi, Ulrike Leiss
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: A growing body of evidence has supported alternatives to sedation and general anesthesia for increasing treatment compliance of children during MRI examinations. Particularities in children with a brain tumor (frequency of examinations, neuropsychological deficits (attention, memory)) have a significant impact on methods of treatment and are given special consideration in this study. OBJECTIVE: The aim of the present study was to (1) evaluate the effectiveness of an MRI training program and to investigate the moderating factors for successful MRI examination for a group of young patients with pediatric brain tumors and/or NF1 and (2) to examine the effect of the training on the patient’s well-being. METHODS: A total of 87 in the retrospective analyses (Study 1) and a subgroup of 17 patients in the prospective analyses (Study 2, ClinicalTrials.gov: NCT04474678) of the neuro-oncology unit with a mean age of 6.83 years underwent a two-step program to prepare children for MRI, including an in vitro strategy training inside the scanner and were recorded using a process-oriented screening. RESULTS: 81 % of the children who had received MRI training managed to successfully undergo the MRI scan. Hence, the rate of successful MRI examinations without anesthesia was almost five times as high in the group that received MRI training compared to the group that did not. Memory, attentional difficulties and hyperactivity were significant neuropsychological moderators for successful or unsuccessful scanning. Furthermore, the training was effective in improving the psychological well-being of the patients. CONCLUSION: Based on the results, the MRI training is an effective alternative to sedation of young patients for MRI examinations and a promising tool for improving patient well-being related to the diagnostic procedure. However, the intervention needs to be customized according to the children’s individual neuropsychological difficulties, which requires specialized psychological staff and an interdisciplinary approach.
Acute kidney injury and its duration in patients treated with radical cystectomy in the Enhanced Recovery After Surgery era: Optimizing the selection of patients for restrictive fluid therapy
Authors: A. Martini, R. Leni, F. Pellegrino, G. Basile, S. Scuderi, M. De Angelis, L. Nocera, G. Rosiello, G. Gandaglia, F. Montorsi, A. Briganti, A. Gallina, M. Moschini
Journal: European Urology (2022)
Increased awareness of surgical outcomes improves long-term functional outcomes after robot-assisted radical prostatectomy. A prospective assessment following implementation of prospective data collection
Authors: G.O. Cirulli, G. Rosiello, S. Scuderi, G. Gandaglia, N. Fossati, E. Mazzone, F. Barletta, V. Cucchiara, D. Robesti, R. Leni, L. Toneatto, L. Quarta, L. Dambrosio, A. Gallina, A. Pellegrino, E. Camisassa, S. Comana, F. Dehò, N. Fossati, A. Martini, G. Colandrea, A. Stabile, F. Montorsi, A. Briganti
Journal: European Urology (2022)
The importance of the long Covid-19 in the evolution of patients with neoplasms.
Authors: Viola Popov, Mihaela Andreescu, Catalina Pirvu, Andra Grigorie, Oana Constantin, Andreea Calen, Mihaela Dana Badoiu Niculae, Adriana Badea, Ana Rus, Lelia Iliescu
Journal: Journal of Clinical Oncology (2022)

e18647 Background: Patients with comorbidities especially those with oncological diseases could have severe COVID-19 outcomes. OBJECTIVE: The aim of this study was to evaluate the role of prolonged positivity of SARS-Cov2 in evolution of patients with various neoplasia. Methods: We analysed clinical and laboratory (hematological parameters and inflammatory markers: interleukin-6 and ferritin) data of COVID-19 patients admitted in intensive care unit (ICU) Department of our hospital, during 2020-2021 and presented in medical history solid tumors or haematological neoplasia . The cohort of patients included 78 patients with severe and critical form of COVID-19, 31 patients with solid tumors and 47 patients with hematologic malignancies. We consider long COVID-19 all cases with SARS Cov2 positivity more than 14 days. Results: The frequency of long COVID-19 was quite equal between patients groups with solid tumors and hematologic malignancies, incidence rate 1:2, the incidence rate differences was 1:18, p = 0.75. Long COVID-19 was observed in 60% cases with favourable evolution, Chi-squared 5.35%, p = 0.02, these patients had moderate form and was admitted in hospital in 1 or more days after the onset, median value 3 (min 1, max 55) compared with patients with normal duration of positivity of SARS-Cov2 test- median value 2 (min 1, max 8), p = 0.01. The Kaplan Meyer survival analyses indicated long COVID-19 as predictive factor for unfavourable evolution, Chi-squared 17.97, p &lt; 0.0001. Although we have not obtain significant differences, we observed more severe lymphopenia in patient without long COVID-19, probably because a part of these patients group died in the first 14 days of COVID-19 (0.765 (min 0.04, max 297.64) vs. 1.01 (min 0.09, max 254.35), p = 0.09). The rest of hematological and biochemistry parameters was not significant different between groups. Infectious and thrombotic complication was most frequent in patients with long COVID-19, Chi squared 8.6, p = 0.003. Conclusions: Long Covid-19 is predictable for unfavourable evolution and is associated with sepsis and thrombotic complication. This diagnosis is frequent in patients who was admitted in hospital after the onset of COVID-19 symptoms, early treatment of COVID-19 in oncological patients being very important for favourable evolution.
EPCT-08. Disease-specific working groups within the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and Children’s Brain Tumor Network (CBTN) facilitate multi-disciplinary collaboration and translation of innovative strategies in pediatric neuro-oncology
Authors: Cassie Kline, Adam Resnick, Michael Prados, Sabine Mueller
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: In Summer 2019, PNOC leadership developed working groups to align basic scientists, clinical researchers, and foundations for rapid translation of novel therapies for children and young adults with central nervous system tumors. Soon after, PNOC partnered with the Children’s Brain Tumor Network (CBTN) to grow collaborations and augment preclinical resources. Since their inception, working groups have advanced translation of new therapies and biomarkers, developed pipelines for preclinical and clinical research, and expanded global collaborations. DESIGN: Each working group is led by 2 to 3 experts in a disease, such as medulloblastoma, diffuse midline glioma, or craniopharyngioma, or subject matter, like imaging, nursing, or diversity, equity, and inclusion. A project manager coordinates regular multidisciplinary meetings to share new findings from research laboratories, provide updates on clinical trial development (with real-time feedback and incorporation of trial endpoints and biomarkers), and invite speakers to share advancements in the disease or subject of interest. RESULTS: Eleven working groups have been created with over 200 members across the United States, Europe, Australia. More than 20 foundations, led predominantly by families, provide support and insight to guide working group efforts. Working groups have developed 4 clinical trials (n=2, diffuse midline glioma; n=1, craniopharyngioma; n=1, medulloblastoma) and completed 3 international surveys, investigating experiences of patients/families affected by craniopharyngioma, evaluating diversity and inclusion throughout the consortia, and assessing nursing and advanced practice provider needs. Additional accomplishments include a registry for atypical teratoid rhabdoid tumors, a population dataset evaluating diversity in clinical research participation across consortia, incorporation of nursing members for review and refinement of clinical trial protocols, and updated imaging case report forms for application across clinical trials. CONCLUSION: Multidisciplinary working groups within international consortia facilitate efficient translation of multi-pronged strategies to improve the care of children and young adults with central nervous system tumors.
Impact of long term indwelling JJ stent on renal parenchyma and estimated glomerular function rate (eGFR)
Authors: N. Branger, V. Lorusso, A. Pacchetti, F. Lannes, D. Sypre, F. Espinosa, C. Manceau, S. Rybikowski, S. Brunelle, T. Maubon, G. Pignot, J. Walz
Journal: European Urology (2022)
INSP-17. Augmented Drug Delivery for Pediatric Diffuse Midline Glioma using Convection Enhanced Delivery
Authors: Mark M Souweidane
Journal: Neuro-Oncology (2022)

Abstract Convection enhanced delivery (CED), an alternative to systemic chemotherapy, spans nearly two decades of clinical experience. The application of CED in pediatric neuro-oncology has been mainly used in children with DMG. This exploratory period is highlighted by widely variable features including procedural technique, disease extent, device interface, infusion parameters, and therapeutic agent. This presentation is meant to critically assess if CED for DMG is a logical therapeutic strategy. Most convincing to the perpetuation of this platform is the reproducible demonstration of augmented drug delivery. Post-treatment ratios of intralesional to systemic drug concentrations consistently exceed 1000. CED in the brain stem satisfies a desirable goal of CNS drug delivery: achieving high target tissue drug concentrations while avoiding systemic exposure. Surgical targeting of the brain stem and cannula deployment are solidly established as safe and accurate. Catheter insertion complications such as clinically relevant hemorrhage, CNS infection, and neurological injury are exceptional. Likewise, targeting error is on a millimeter scale with infrequent need for catheter repositioning. The use of intrinsic MRI signals, direct drug labeling, and surrogate tracers have all been used for measuring distribution of the infusion. The experience using a radio-labelled theragnostic agent has provided detailed distribution and dosimetry information. Based on estimates of tumor and hence target volumes, a rationale goal is to reach volumes of distribution in the range of 15-25 cm3. Optimizing this goal has focused on surgical targeting, infusion duration, and multiple treatment plans. Computational predictive modeling is being employed as a preoperative adjunct for maximizing distribution. Experience in DMG thus far has been limited to feasibility and safety studies. There is a paucity of Phase 2 studies and hence outcome has not yet been rigorously tested. Anecdotal increase in survival and long-term survival has been reproducibly reported. Of particular interest are the occasional cases of children exhibiting late out-of-treatment field and even extra-CNS recurrence. Available data is convincing that CED should serve be further explored in future clinical trials designs for children with DMG. Important features of any Phase 2 study design however should include monitoring of drug distribution, measures of tumor coverage, early response monitoring techniques, and possibly combination with whole CNS axis treatment.
Rapid and high-throughput testing of antifungal susceptibility using an AIEgen-based analytical system
Authors: Xiaoxue Ge, Meng Gao, Bairong He, Nannan Cao, Kerun Li, Yong Liu, Sanmei Tang, Kai Liu, Jing Zhang, Fang Hu, Lei Zheng, Bo Situ
Journal: Biomaterials (2022)
Negative hyperselection for mutations associated with anti-EGFR antibody resistance in <i>RAS</i> wildtype metastatic colorectal cancer (mCRC): Evaluation of the PANAMA trial (AIO-KRK-0212, maintenance therapy with 5-FU, folinic acid (FU/FA) with or without panitumumab).
Authors: Andreas Jay Kind, Dominik Paul Modest, Christine Sers, Soulafa Mamlouk, Meinolf Karthaus, Stefan Fruehauf, Ullrich Graeven, Ludwig Fischer Von Weikersthal, Eray Goekkurt, Anke C. Reinacher-Schick, Stefan Kasper, Annika Kurreck, Beeke Hoppe, Swantje Held, Volker Heinemann, David Horst, Armin Jarosch, Sebastian Stintzing, Tanja Trarbach, Arndt Stahler
Journal: Journal of Clinical Oncology (2022)

3536 Background: We evaluated the prognostic and predictive impact of DNA mutations related to anti-EGFR antibody resistance in patients of the PANAMA trial, which compared Panitumumab (Pmab) and FU/FA versus FU/FA maintenance therapy after Pmab-FOLFOX induction therapy in RAS wild-type (wt) mCRC. Methods: Next generation panel sequencing was conducted on 201 of 248 tumors obtained prior to study inclusion from the full analysis set using the Cancer Hotspot Panel v2 on an Illumina MiSeq system. Hyperselection covered mutations of the following genes: KRAS, NRAS, BRAF, HER2, PTEN, AKT1, PIK3CA. Median progression-free (PFS) and overall survival (OS) since start of maintenance were estimated by Kaplan-Meier and Cox-regression (log rank test). Objective response rates (ORR) of maintenance therapy were compared by Chi-square-test. Results: From 201 tumors, 41 (20.4 %) carried at least one mutation: KRAS: 7 (3.5%), BRAF: 23 (11.4%), PTEN: 4 (2.0%), AKT1: 2 (1.0%), PIK3CA: 12 (6.0%), with 6 tumors harboring co-occuring mutations. No mutations were found in NRAS and HER2. Negative hyperselection (wt for all genes) was associated with (numerically) favourable prognosis in terms of PFS (HR 0.79 (95% CI 0.55 – 1.12), p=0.184), OS (HR 0.61 (95% CI 0.40 – 0.95), p=0.028) and ORR (39.4% vs. 29.3%, p=0.279). The benefit of adding Pmab to FU/FA during maintenance was limited to the hyperselection wt subgroup, with significantly longer PFS (9.9 vs. 6.0 months, 0.64 (95% CI 0,46 – 0.90), p = 0.011), numerically longer OS and significantly higher ORR (49.4% vs 26.6%, p=0.009) compared to FU/FA (Table). Conclusions: Mutations related to resistance concerning anti-EGFR antibodies were detected in 41 of 201 (20.4%) of analysed tumors and associated with a worse prognosis compared to hyperselected wt tumors. Negative hyperselection may aid in the identification of patients with relevant benefit from maintenance therapy including Pmab. [Table: see text]
The impact of pre-treatment plasma sex hormones on the immune checkpoint inhibitors response to metastatic non-small cell lung cancer.
Authors: Yumeng Zhang, Lancia Darville, Stephanie Hogue, Julie E. Hallanger-Johnson, Youngchul Kim, Jhanelle Elaine Gray, Lary A. Robinson
Journal: Journal of Clinical Oncology (2022)

e21088 Background: Immune checkpoint inhibitors (ICI) have changed the outcomes in metastatic non-small cell lung cancer (mNSCLC). The immune system partially determines the response to ICI. The impact of sex hormones on immune responses is well recognized in autoimmune disease and vaccine response. Little is known about the interplay between the sex hormones and the response to ICI in mNSCLC. Methods: This prospective, observational study included patients with mNSCLC at Moffitt Cancer Center who received ICI as monotherapy or combination with chemotherapy. Plasma was collected before the first ICI infusion. Extraction and detection of the hormones were optimized by modifying the previous method. Hormone levels were measured using ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). Estrogens included propyl pyrazole triol (PPT), 17β-estradiol (E2), and S-equol. Androgens included 5-androstenediol, 3β-androstenediol (3β-diol), and dehydroepiandrosterone (DHEA).Patients were divided based on clinical benefits, defined as a complete or partial response or stable disease for at least 12 months. Categorical variables were compared using the Chi-square test or Fischer exact test; continuous variables were compared using the Mann-Whitney U test. Results: Sixty-one patients were included and 50.8% were female. The median age was 67 years. Twenty-eight patients had clinical benefits from ICI. Patients in the clinical benefit group had higher BMI. The clinical benefit group had significantly lower androgen levels but no difference in estrogen levels. The median DHEA level was 3.7 ng/ml in the clinical benefit group and 9.6 ng/ml in the group without (p &lt; 0.001). The 5-Androstenediol was also lower in the clinical benefits group (table I). When normalized to the age/sex-adjusted reference range, the difference of DHEA and 5-androstenediol was retained (p &lt; 0.001 and 0.014, respectively). 3β-diol was below the limit of detection. Conclusions: The serum DHEA and 5-androstenediol levels were lower in mNSCLC patients who benefited from ICI, regardless of sex. Larger studies are needed to confirm the role of pre-treatment androgens levels as negative biomarkers for ICI response. [Table: see text]
Immunotherapy-based combinations in the first-line treatment of metastatic renal cell carcinoma with sarcomatoid features: A systematic review and network meta-analysis
Authors: F. Quhal, K. Mori, E. Laukhtina, P. Rajwa, H. Mostafaei, B. Pradere, S.F. Shariat, M. Schmidinger
Journal: European Urology (2022)
Dysthyroidism during immune checkpoint inhibitors is associated with improved overall survival in solid tumors: Data-mining of 1,382 electronic patient records.
Authors: Mathilde Beaufils, Vincent Amodru, Manuel Tejeda, Brice Chanez, Anne Sophie Chretien, Gwenaelle Gravis, Anne Madroszyk, Anthony Goncalves, Aaron E. Lisberg, Daniel Olive, Louis Tassy, Frédéric Castinetti, Philippe Rochigneux
Journal: Journal of Clinical Oncology (2022)

2659 Background: Medical treatment of solid tumors cancer has irreversibly changed since the development of immune checkpoint inhibitors (ICI). However, immune-related adverse events (irAE) are challenging in routine practice. Dysthyroidism is the most common endocrine irAE and small series suggest that dysthyroidism might be associated with ICI efficacy. This led us to explore the association between ICI-induced dysthyroidism and overall survival (OS) in a large cohort of solid tumor patients (pts) using data mining of electronic patient records (EPR). Methods: ConSoRe is a new generation data analytics solution using natural language processing to search aggregated data and perform advanced data mining. It was used for data extraction from EPR of pts treated with ICI for solid tumors in Institut Paoli-Calmettes (Marseille Cancer Center, France), with validation using manual screening of 28.8% EPR. All dysthyroidism were verified and only dysthyroidism ICI-induced were retained. Survival analyses were performed by Kaplan-Meier method and compared using the log-rank test (survminer R package). In the uni/multivariate analysis, the Cox proportional-hazards model was used to estimate the variables associated with OS, using hazard ratio (HR) and its associated 95% confidence interval. Results: Data extraction identified 1,385 pts treated with ICI in 2011-2021. Dysthyroidism was observed in 90 pts (6.5%), including 22 hyperthyroidism (24%), 36 hypothyroidism (40%) and 32 hyperthyroidism and hypothyroidism (36%). In this cohort, 81 % of the dysthyroidism were related to PD(L)-1 inhibitors and 19 % to CTLA-4/PD(L)-1 inhibitors combination. No statistical difference was observed in term of tumor location between patients with or without dysthyroidism. Dysthyroidism was associated with improved OS (HR=0.46, 95%CI 0.29-0.70, p=0.0005) with a median OS of 65 months (mo) vs. 30 mo in patients without dysthyroidism. Survival impact of dysthyroidism was consistent using a 2-mo landmark analysis, fixed on median time to dysthyroidism. In multivariate analysis including sex, age, tumor localization, line numbers and type of ICI, dysthyroidism was independently associated with an improved OS (HR=0.49, 95%CI 0.32-0.75, p=0.001), as presented in the Table. Conclusions: Data mining identified a large number ICI-induced dysthyroidism, associated with an improved OS. The onset of dysthyroidism might help oncologist detecting patients more likely to benefit from ICI. [Table: see text]
Stage 1 results of BrUOG 354: A randomized phase II trial of nivolumab alone or in combination with ipilimumab for people with ovarian and other extra-renal clear cell carcinomas (NCT03355976).
Authors: Don S. Dizon, Katina Robison, Shannon Diane MacLaughlan David, Jason T Machan, Matthew James Hadfield, Eric I Marks, Rani Chudasama, Tarra Evans, Mary Lorraine Lopresti, Emma Safran, Michaela Kastura, Faith Hassinger, Ashlee Sturtevant, Roxanne Wood, Alexi A. Wright, Rochelle Strenger, Ursula A. Matulonis, Christina Bandera, Susana M. Campos, Michael J. Birrer
Journal: Journal of Clinical Oncology (2022)

5598 Background: Clear Cell Carcinoma (CCC) outside the kidney is a rare tumor that can arise from multiple organs, including the ovary, endometrium and cervix. Extra-renal CCC is chemoresistant and has a poor prognosis. Data suggest that CCC of the gynecologic tract resembles the genomic profile of Renal Cell Carcinoma (RCC), which is responsive to immune checkpoint inhibition (ICI) therapy. We are conducting a two-stage phase 2 trial evaluating immunotherapy for extra-renal CCC. The primary objective is to assess overall rate of response (ORR); Progression-Free (PFS), Overall Survival (OS), and correlative biomarker studies are secondary. Here we present the results of Stage 1. Methods: This is a randomized two-stage non-comparative phase II study evaluating nivolumab (240mg IV every two weeks) alone (N) and in combination with ipilimumab (1mg/kg every six weeks, [N+I]) in patients with relapsed extra-renal CCC after at least one prior chemotherapy (no prior ICI), and measurable disease. Treatment was continued until disease progression or unacceptable toxicity. Stage 1 of this trial called for up to 30 volunteers (15 per arm) after which the study was closed. Consideration to reopen to stage 2 called for two or more responses in either arm. Here we present the completion of Stage 1; the release of results was approved by Brown University Oncology Group (BrUOG) Data Safety and Monitoring Committee. Results: Between July 2018 and October 2021, 30 patients were enrolled and 29 were treated (Table). The majority (83%) had CCC of the ovary (n=24). The ORR with N and N+I was 14.2 and 26.7%, respectively. The 6 month PFS rate was 19.1 and 43.8%; median PFS was 2.7 (95%CI 1.3-5.1) and 5.1 months (95%CI 0.9-NR), respectively. Grade ≥3 treatment-related toxicities occurred in 4 (28.6%) on N and 5 (33.3%) on N+I. There were no treatment-related deaths and no new safety signals. One volunteer enrolled on N+I stopped treatment after two years and remains in CR to date. Conclusions: Although sufficient activity was seen in CCC in both arms, the single-agent activity of N is similar to published reports in platinum-resistant epithelial ovarian cancer and decision made not to pursue it further. However, the combination of ipilimumab and nivolumab warrants additional investigation, and the second stage of this study will enroll 14 more patients to receive N+I. Clinical trial information: NCT03355976. [Table: see text]